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Based on aqueous redox chemistry and simple in vivo models of oxidative stress, Escherichia coli and Saccharomyces cerevisiae, the cationic Mn(III) N-substituted pyridylporphyrins (MnPs) have been identified as the most potent cellular redox modulators within the porphyrin class of drugs; their efficacy in animal models of diseases that have oxidat...
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... (metallocorroles, metallotexaphyrins, Mn salen derivatives and Mn cyclic polyamines) [for details, see also [6][7][8][9][10] . In addi- tion, simple metal salts and oxides, such as manganese salts, cerium dioxide (CeO 2 ), osmium tetroxide (OsO 4 ) and Pt nanoparticles are potent SOD mimics and have been explored for efficacy in in vivo studies ( fig. 2 ) [8,[11][12][13] . Few compounds are redox active but do not bear metals, such as nitroxides, ni- trones, mitochondria-targeted ubiquinone and its derivatives [8,9,[14][15][16] ...
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... now involved in the development of metalloporphyrins and in the exploration of the mechanistic aspects of their mode(s) of action(s) [33][34][35][36][37][38][39][40][41][42][43][44][45] . The modification of the porphyrin core by enlargement (texaphyrins) and shrinkage (corroles) has been explored by Sessler's and Gross's groups, respectively ( fig. 2 ) [46][47][48][49][50][51][52][53][54] . Mahammed and Gross [51] have shown that metal complexes of 'shrinked' porphyrins -metallocorroles -due to their enhanced stability in a higher +4 oxidation state than that of porphyrins possess a fair catalase-like in addition to SOD- like activity [46] ...
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Two novel porphyrin dyes (Q1 and Q2) bearing alkoxyl chains with a carbazole moiety as the electron donor have been synthesized and utilized as sensitizers for dye-sensitized solar cells (DSSCs). Compared with Q2, the molecule of Q1 has an additional ethynylene bridge between the carbazole moiety and the porphyrin framework. Photophysical and elect...
We elucidate the role of the ligand in determining the ion pair structure of the [(NAC)Au(η2-3-hexyne)]+ BF4‒ [(NAC = Nitrogen Acyclic Carbene, also known as ADC = Acyclic Diamino Carbene)] catalysts and how the position of the anion influences their catalytic performances, giving a detailed relationship between the ion pairs structure, determined...
Citations
... In addition, Celikoglu et al. [70] demonstrated that VE alleviated the oxidative stress induced by mercury, causing increased activities of SOD, catalase, and glutathione peroxidase. Furthermore, α-Toc supplementation resulted in a protective effect against oxidative brain damage through a reduction in lipid peroxidation and improved brain antioxidant capacity by increasing GSH levels [71,72]. ...
With the advancement of in vivo studies and clinical trials, the pathogenesis of neurodegenerative diseases has been better understood. However, gaps still need to be better elucidated, which justifies the publication of reviews that explore the mechanisms related to the development of these diseases. Studies show that vitamin E supplementation can protect neurons from the damage caused by oxidative stress, with a positive impact on the prevention and progression of neurodegenerative diseases. Thus, this review aims to summarize the scientific evidence of the effects of vitamin E supplementation on neuroprotection and on neurodegeneration markers in experimental models. A search for studies published between 2000 and 2023 was carried out in the PubMed, Web of Science, Virtual Health Library (BVS), and Embase databases, in which the effects of vitamin E in experimental models of neurodegeneration were investigated. A total of 5669 potentially eligible studies were identified. After excluding the duplicates, 5373 remained, of which 5253 were excluded after checking the titles, 90 articles after reading the abstracts, and 11 after fully reviewing the manuscripts, leaving 19 publications to be included in this review. Experiments with in vivo models of neurodegenerative diseases demonstrated that vitamin E supplementation significantly improved memory, cognition, learning, motor function, and brain markers associated with neuroregeneration and neuroprotection. Vitamin E supplementation reduced beta-amyloid (Aβ) deposition and toxicity in experimental models of Alzheimer’s disease. In addition, it decreased tau-protein hyperphosphorylation and increased superoxide dismutase and brain-derived neurotrophic factor (BDNF) levels in rodents, which seems to indicate the potential use of vitamin E in preventing and delaying the progress of degenerative lesions in the central nervous system.
... Immunoreactivity of the oxidative stress biomarker, HNE, was significantly reduced in the BuOE-treated flight group compared to the flight saline group. This suggests that BuOE was effective in reducing reactive oxygen species that activate retinal stress responses during space flight [49,50]. Metalloporphyrin catalytic antioxidants are potent detoxifiers of lipid peroxides and lipoperoxyl radicals, a process that is mediated via hydroxyl radicals [6,51]. ...
The goal of the present study was to characterize acute oxidative damage in ocular structure and retinal function after exposure to spaceflight, and to evaluate the efficacy of an antioxidant in reducing spaceflight-induced changes in the retina. Ten-week-old adult C57BL/6 male mice were flown aboard the ISS on Space-X 24 over 35 days, and returned to Earth alive. The mice received a weekly injection of a superoxide dismutase mimic, MnTnBuOE-2-PyP 5+ (BuOE), before launch and during their stay onboard the ISS. Ground control mice were maintained on Earth under identical environmental conditions. Before the launch, intraocular pressure (IOP) was measured using a handheld tonometer and retinal function was evaluated using electroretinogram (ERG). ERG signals were recorded when the mouse eye was under dark-adapted conditions in response to ultraviolet monochromatic light flashes. Within 20 h after splashdown, IOP and ERG assessments were repeated before euthanasia. There were significant increases in body weight for habitat control groups post-flight compared to pre-flight measurements. However, the body weights were similar among flight groups before launch and after splashdown. The IOP measurements were similar between pre- and post-flight groups with no significant differences between BuOE-treated and saline controls. Immunofluorescence evaluation showed increases in retinal oxidative stress and apoptotic cell death after spaceflight. BuOE treatment significantly decreased the level of the oxidative stress biomarker. ERG data showed that the average amplitudes of the a- and b-wave were significantly decreased (39% and 32% by spaceflight, respectively) compared to that of habitat ground controls. These data indicate that spaceflight conditions induce oxidative stress in the retina, which may lead to photoreceptor cell damage and retinal function impairment.
... The observed prooxidant action was also dose-dependent. It has recently been shown that, in some cases, metalloporphyrins exhibit both antioxidant [42,[74][75][76] and prooxidant properties [46,47,77,78], depending on environmental conditions, such as the presence of the other reagents in the system [44], the level of reactive oxygen species, the availability of oxygen, etc. [47]. According to the UV-Vis and luminescence spectroscopy data (see Section 3.2), upon intercalation, the electronic properties of porphyrins changed due to their interaction with the densely packed metal hydroxide layers. ...
In this study, organo-inorganic nanohybrids LHGd-MTSPP with enzyme-like activity were prepared by in situ intercalation of anionic 5,10,15,20-tetrakis-(4-sulfonatophenyl)porphyrin and its complexes with Zn(II) and Pd(II) (MTSPP, M = 2H, Zn(II) and Pd(II)) into gadolinium layered hydroxide (LHGd). The combination of powder XRD, CHNS analysis, FT-IR, EDX, and TG confirmed the layered structure of the reaction products. The basal interplanar distances in LHGd-MTSPP samples were 22.3–22.6 Å, corresponding to the size of an intercalated tetrapyrrole molecule. According to SEM data, LHGd-MTSPP hybrids consisted of individual lamellar nanoparticles 20–50 nm in thickness. The enzyme-like activity of individual constituents, LHGd-Cl and sulfoporphyrins TSPP, ZnTSPP and PdTSPP, and hybrid LHGd-MTSPP materials, was studied by chemiluminescence analysis using the ABAP/luminol system in phosphate buffer solution. All the individual porphyrins exhibited dose-dependent antioxidant properties with respect to alkylperoxyl radicals at pH 7.4. The intercalation of free base TSPP porphyrin into the LHGd preserved the radical scavenging properties of the product. Conversely, in LHGd-MTSPP samples containing Zn(II) and Pd(II) complexes, the antioxidant properties of the porphyrins changed to dose-dependent prooxidant activity. Thus, an efficient approach to the design and synthesis of advanced LHGd-MTSPP materials with switchable enzyme-like activity was developed.
... In our studies, we have decided to use MnP (MnTnBuOE-2-PyP 5+ ), also known as BMX-001, since it has advanced towards clinical trials. It is moderately lipophilic and distributes to high levels in cells and cellular fragments, most so in mitochondria [28]. MnP has been shown to have an excellent safety profile in preclinical setting and clinical trials and acted as tumor radioand chemosensitizer in cellular and animal models. ...
We have employed a redox-active MnP (MnTnBuOE-2-PyP5+, Mn(III) meso-tetrakis (N-n-butoxyethylpyridinium-2-yl) porphyrin) frequently identified as superoxide dismutase mimic or BMX-001, to explore the redox status of normal ovarian cell in relation to two ovarian cancer cell lines: OV90 human serous ovarian cancer cell and chemotherapy-resistant OV90 cell (OVCD). We identified that OVCD cells are under oxidative stress due to high hydrogen peroxide (H2O2) levels and low glutathione peroxidase and thioredoxin 1. Furthermore, OVCD cells have increased glycolysis activity and mitochondrial respiration when compared to immortalized ovarian cells (hTER7) and parental cancer cells (OV90). Our goal was to study how ovarian cell growth depends upon the redox state of the cell; hence, we used MnP (BMX-001), a redox-active MnSOD mimetic, as a molecular tool to alter ovarian cancer redox state. Interestingly, OVCD cells preferentially uptake MnP relative to OV90 cells which led to increased inhibition of cell growth, glycolytic activity, OXPHOS, and ATP, in OVCD cells. These effects were further increased when MnP was combined with carboplatin. The effects were discussed with regard to the elevation in H2O2 levels, increased oxidative stress, and reduced Nrf2 levels and its downstream targets when cells were exposed to either MnP or MnP/carboplatin. It is significant to emphasize that MnP protects normal ovarian cell line, hTER7, against carboplatin toxicity. Our data demonstrate that the addition of MnP-based redox-active drugs may be used (via increasing excessively the oxidative stress of serous ovarian cancer cells) to improve cancer patients’ chemotherapy outcomes, which develop resistance to platinum-based drugs.
... Several manganese porphyrins, such as Mn III meso-tetrakis(4carboxyphenyl)porphyrin (MnTCPP + ), have been applied for treating of oxidative stress injuries and inflammation 9,10 . However, the catalytic activity of MnTCPP + is quite low due to the negative metal-centered redox potential (E 1/2 = −194 mV versus normal hydrogen electrode (NHE)) 11,12 , as its four benzoyloxys are strong electron-donating groups after deprotonation. ...
Constructing nanomaterials mimicking the coordination environments of natural enzymes may achieve biomimetic catalysis. Here we construct a two-dimensional (2D) metal-organic framework (MOF) nanosheet catalyst as an artificial antioxidase for nanocatalytic rheumatoid arthritis treatment. The 2D MOF periodically assembles numbers of manganese porphyrin molecules, which has a metal coordination geometry analogous to those of two typical antioxidases, human mitochondrial manganese superoxide dismutase (Mn-SOD) and human erythrocyte catalase. The zinc atoms of the 2D MOF regulate the metal-centered redox potential of coordinated manganese porphyrin ligand, endowing the nanosheet with both SOD- and catalase-like activities. Cellular experiments show unique anti-inflammatory and pro-biomineralization performances of the 2D MOF, while in vivo animal model further demonstrates its desirable antiarthritic efficacy. It is expected that such a nanocatalytic antioxidation concept may provide feasible approaches to future anti-inflammatory treatments.
... PPIX is a precursor in the synthesis of essential prosthetic tetraporphyrin groups such as heme and Chl. Porphyrins have considerable potential in biomedical applications as drug precursors and modulators of cancer cell growth (Tovmasyan et al., 2013). ...
Tetrapyrroles are essential metabolic components produced by almost all organisms, and they participate in various fundamental biological processes. Tetrapyrroles are used as pharmaceuticals, food additives, and nutraceuticals, as well as in agricultural applications. However, their production is limited by their low extraction yields from natural resources and by the complex reaction steps involved in their chemical synthesis. Through advances in metabolic engineering and synthetic biology strategies, microbial cell factories were developed as an alternative method for tetrapyrrole production. Herein, we review recent developments in metabolic engineering and synthetic biology strategies that promote the microbial production of high-value compounds in the tetrapyrrole biosynthesis pathway (e.g., 5-aminolevulinic acid, heme, bilins, chlorophyll, and vitamin B12). Furthermore, outstanding challenges to the microbial production of tetrapyrrole compounds, as well as their possible solutions, are discussed.
... Reducing oxidative stress by increasing SOD activity has proven beneficial to the maintenance of BBB integrity in both in vivo and in vitro models [190,191]. Manganese porphyrin compounds are a particular class of SOD mimetics that exert anti-inflammatory effects through the blockade of transcription factors NF-κB and HIF-1α [192][193][194]. The manganese porphyrin compound BMX-001, is currently in a phase 2 trial in combination with temozolomide and radiotherapy for the treatment of high-grade gliomas or multiple brain metastases, in efforts to ameliorate the deterioration of cognitive outcomes and quality of life [ [188,195], NCT02655601, NCT03608020]. ...
Exposure to radiation during the treatment of CNS tumors leads to detrimental damage of the blood brain barrier (BBB) in normal tissue. Effects are characterized by leakage of the vasculature which exposes the brain to a host of neurotoxic agents potentially leading to white matter necrosis, parenchymal calcification, and an increase chance of stroke. Vasculature of the blood tumor barrier (BTB) is irregular leading to poorly perfused and hypoxic tissue throughout the tumor that becomes resistant to radiation. While current clinical applications of cranial radiotherapy use dose fractionation to reduce normal tissue damage, these treatments still cause significant alterations to the cells that make up the neurovascular unit of the BBB and BTB. Damage to the vasculature manifests as reduction in tight junction proteins, alterations to membrane transporters, impaired cell signaling, apoptosis, and cellular senescence. While radiotherapy treatments are detrimental to normal tissue, adapting combined strategies with radiation targeted to damage the BTB could aid in drug delivery. Understanding differences between the BBB and the BTB may provide valuable insight allowing clinicians to improve treatment outcomes. Leveraging this information should allow advances in the development of therapeutic modalities that will protect the normal tissue while simultaneously improving CNS tumor treatment.
... (2017) have evaluated the effect of a lipophilic Mn porphyrin (MnP)-based SOD mimic, MnTnBuOE-2-PyP 5+ (BMX-001), administered subcutaneously for one week before cranial irradiation and continued for one week afterward, in the radioprotection of hippocampal neurogenesis in a mouse model [154], and obtained promising results. Accordingly, MnTnHex-2-PyP 5+ , a similar SOD mimetic compound [155], delayed the onset of radiation-induced lung lesions, reduced respiratory-rate elevation and lessened the pathologic increases in lung weight in a model of radiation-induced lung injury in a non-human primate [156]. More recently, the MnP SOD mimetic AEOL 10150, also known as MnTDE-2-ImP 5+ , showed promising results in a whole thoracic lung irradiation model in nonhuman primates [157][158][159]. ...
Superoxide dismutases (SODs) are metalloenzymes that play a major role in antioxidant defense against oxidative stress in the body. SOD supplementation may therefore trigger the endogenous antioxidant machinery for the neutralization of free-radical excess and be used in a variety of pathological settings. This paper aimed to provide an extensive review of the possible uses of SODs in a range of pathological settings, as well as describe the current pitfalls and the delivery strategies that are in development to solve bioavailability issues. We carried out a PubMed query, using the keywords “SOD”, “SOD mimetics”, “SOD supplementation”, which included papers published in the English language, between 2012 and 2020, on the potential therapeutic applications of SODs, including detoxification strategies. As highlighted in this paper, it can be argued that the generic antioxidant effects of SODs are beneficial under all tested conditions, from ocular and cardiovascular diseases to neurodegenerative disorders and metabolic diseases, including diabetes and its complications and obesity. However, it must be underlined that clinical evidence for its efficacy is limited and consequently, this efficacy is currently far from being demonstrated.
... The treatment with MnP/ascorbate was thus far only investigated in cellular and mouse models of breast and ovarian cancers in combination with chemo-and radiotherapy. Figure 3: Therapeutic effects of MnTnBuOE-2-PyP 5+ in suppressing cancer and protecting normal tissue [3,4,12,24,43,54,56,58,60,82,93,100,101,[114][115][116][117][118][119][120][121][122]. Such effects are driving progress of MnTnBuOE-2-PyP 5+ into clinical trials. ...
Mn(III) ortho-N-alkyl- and N-alkoxyalkyl porphyrins (MnPs) were initially developed as superoxide dismutase (SOD) mimics. These compounds were later shown to react with numerous reactive species (such as ONOO-, H2O2, H2S, CO3•-, ascorbate, and GSH). Moreover, the ability of MnPs to oxidatively modify activities of numerous proteins has emerged as their major mechanism of action both in normal and in cancer cells. Among those proteins are transcription factors (NF-κB and Nrf2), mitogen-activated protein kinases, MAPKs, antiapoptotic bcl-2, and endogenous antioxidative defenses. The lead Mn porphyrins, namely, MnTE-2-PyP5+ (BMX-010, AEOL10113), MnTnBuOE-2-PyP5+ (BMX-001), and MnTnHex-2-PyP5+, were tested in numerous injuries of normal tissue and cellular and animal cancer models. The wealth of the data led to the progression of MnTnBuOE-2-PyP5+ into four Phase II clinical trials on glioma, head and neck cancer, anal cancer, and multiple brain metastases, while MnTE-2-PyP5+ is in Phase II clinical trial on atopic dermatitis and itch.
... This catalytic cycle is obviously modulated by the redox potential of the metal site [92]. The antioxidant efficiency of MnPs in vivo depends on their bioavailability, i.e., tissue, cellular, and subcellular distribution, and the nature of N-pyridyl substituents, which can alter their charge, size, shape, and lipophilicity [98,[101][102][103]. ...
Reactive oxygen species and reactive nitrogen species are highly implicated in kidney injuries that include acute kidney injury, chronic kidney disease, hypertensive nephropathy, and diabetic nephropathy. Therefore, antioxidant agents are promising therapeutic strategies for kidney diseases. Catalytic antioxidants are defined as small molecular mimics of antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, and some of them function as potent detoxifiers of lipid peroxides and peroxynitrite. Several catalytic antioxidants have been demonstrated to be effective in a variety of in vitro and in vivo disease models that are associated with oxidative stress, including kidney diseases. This review summarizes the evidence for the role of antioxidant enzymes in kidney diseases, the classifications of catalytic antioxidants, and their current applications to kidney diseases.
